Advances in our basic understanding of the receptor/ligand interactions that regulate T cell activation provide an opportunity to develop new strategies for inducing potent immune responses to tumors. Promising results have been obtained in experimental models in which melanoma tumors have been engineered to express B7 which is an important costimulator of T cell activation. We are testing an alternative approach based on immunization with reconstituted tumor membranes containing additional membrane proteins included to increase immunogenicity and the induction of tumor-specific immunity. Our preliminary results demonstrate that complete protection can be induced in syngeneic mice challenged with the K1735 melanoma after immunization with small unilamellar liposomes composed of reconstituted tumor membranes and purified, recombinant B7. Recent studies suggest that CD40 ligand (CD40L) can also serve as a potent costimulator of T cell activation. We propose pilot experiments designed to determine whether recombinant CD40L can enhance the immunogenicity of K1735 membranes.